This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Prader-Willi Syndrome-PWS is a neurobehavioral syndrome whose clinical features include neonatal failure-to-thrive, a distinct behavioral phenotype, cognitive impairment, hypotonia, hyperphagia and morbid obesity. This syndrome is the most commonly recognized genetic cause of obesity. It has been suggested that the hyperphagia is secondary to altered hypothalamic function, which is a consequence of the genetic alterations that characterize this condition. Children with PWS have evidence of a growth hormone-GH deficiency secondary to hypothalamic dysfunction. Studies have shown that children with PWS treated with GH have a decrease in fat mass and an increase in lean body mass, as well as an increase in growth velocity and in resting energy expenditure. It is currently unknown if treatment of children with PWS with GH causes changes in the hypothalamus, or if the effects are solely peripheral. This study will investigate the effects of GH on hypothalamic recognition of hunger and satiety, as well as on the basal metabolic rate and body composition of PWS individuals. We will compare the neuroanatomical correlates of hunger and satiation using functional MRI-fMRI on PWS patients before and one year after GH treatment. We will use normal weight siblings and non-PWS obese individuals as additional comparison groups. Blood will be drawn to determine various hormonal and neurotransmitter levels at times correlating with hunger and satiety in these individuals. Basal metabolic rate-BMR and body composition via dual energy X-ray absorptiometry-DEXA will be assessed for all individuals, and will be reevaluated in PWS subjects one year after treatment with GH.